Oct1 regulates cell growth of LNCaP cells and is a prognostic factor for prostate cancer
Oct1 regulates cell growth of LNCaP cells and is a prognostic factor for prostate cancer
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DOI：
10.1002/ijc.26043
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发表时间：
2012-03-01
影响因子：
6.4
通讯作者：
Inoue, Satoshi
中科院分区：
文献类型：
--
作者：
Obinata, Daisuke;Takayama, Ken-ichi;Inoue, Satoshi
雄激素受体（AR）在前列腺癌的发生发展中起着至关重要的作用。AR共调节因子表达的改变导致AR超敏反应，这是前列腺癌进展为去势抵抗状态的机制之一。Octamer转录因子1 （Oct1）是pou同源结构域家族中普遍存在的成员，作为AR的共调节因子。在我们的研究中，我们研究了Oct1对前列腺癌发展的贡献。免疫细胞化学分析显示，Oct1在LNCaP细胞的细胞核中表达。sirna介导的Oct1表达沉默抑制LNCaP细胞增殖。102例前列腺癌患者肿瘤标本中Oct1表达的免疫组化分析显示，Oct1免疫反应性与高Gleason评分和AR免疫反应性呈正相关（p = 0.0042和p < 0.0001）。此外，Oct1免疫反应性高的患者癌症特异性生存率较低，Oct1和AR免疫反应性均高的患者癌症特异性预后较差。多因素风险分析显示，高Oct1免疫反应性与较差的癌症特异性生存之间存在显著相关性（p = 0.012）。这些结果表明，Oct1可能是前列腺癌的一个预后因素，作为AR的共同调节因子，并可能导致前列腺癌新的治疗干预措施的发展。
The androgen receptor (AR) plays a critical role in the development and the progression of prostate cancer. Alterations in the expression of AR coregulators lead to AR hypersensitivity, which is one of the mechanisms underlying the progression of prostate cancer into a castrate-resistant state. Octamer transcription factor 1 (Oct1) is a ubiquitous member of the POU-homeodomain family that functions as a coregulator of AR. In our study, the contribution of Oct1 to prostate cancer development was examined. Immunocytochemistry analysis showed that Oct1 is expressed in the nuclei of LNCaP cells. siRNA-mediated silencing of Oct1 expression inhibited LNCaP cell proliferation. Immunohistochemical analysis of Oct1 expression in tumor specimens obtained from 102 patients with prostate cancer showed a positive correlation of Oct1 immunoreactivity with a high Gleason score and AR immunoreactivity (p = 0.0042 and p < 0.0001, respectively). Moreover, patients with high immunoreactivity of Oct1 showed a low cancer-specific survival rate, and those patients with high immunoreactivities of both Oct1 and AR exhibited poorer cancer-specific prognosis. Multivariate hazard analysis revealed a significant correlation between high Oct1 immunoreactivity and poor cancer-specific survival (p = 0.012). These results demonstrate that Oct1 can be a prognostic factor in prostate cancer as a coregulator of AR and may lead to the development of a new therapeutic intervention for prostate cancer.